Pharmaceutically active substances of biopharmaceutical class II (BCS class II) and in particular statins are considered to be unstable under pharmaceutical aspects and are especially susceptible to oxidative degradation. Various methods and procedures are known for preventing this, including a suitable choice of the dosage form, a formulation that uses suitable excipients and selecting a suitable packaging.
To reduce the rate of oxidative degradation of substances of biopharmaceutical class II, in particular statins, they are formulated together with antioxidatively active substances (antioxidants). The active ingredient is adequately stabilized by the antioxidants as well as additional excipients in the pharmaceutical composition, usually an oral form.
One disadvantage here is that measures which are redundant under some circumstances are taken to stabilize the active ingredient. For example the dosage forms known from the prior art contain a quantity of excipient that may have negative effects on the weight and volume of the dosage form as well as the manufacturing costs due to the amount involved. The greater the amount of excipient, the lower at the same time is the concentration of the active ingredient in the formulation. Low active ingredient concentrations have the effect that the amount of impurities, for example, degradation products of the active ingredient is increased in relation to the active ingredient. There in general a high active ingredient concentration, i.e., a small amount of excipients is the goal in the formulation.
In the case of substances of biopharmaceutical class II, in particular statins, however, an important aspect that must also be considered is the fact that the solubility and/or the dissolving rate of these substances in the physiological system is elevated, the greater the proportion of excipients used in the dosage form.
The pharmaceutically active substances are to be understood as those belonging to the pharmacological substance classes of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors. Statins are used mainly as anticholesterolemics in fat metabolism disorders and have the greatest potency relative to all drugs that influence the lipid metabolism.
So far, statin drugs have been available in the form of tablets which have a coating (so-called film-coated tablets). For stabilization of statins, they are formulated together with antioxidatively active substances which may be classified primarily with the chain terminators, reductants, radical scavengers or complexing agents. Thus the formulations known from the prior art usually contain organic acids (e.g., citric acid, salicylic acid), phenols and phenol ethers (e.g., butyl hydroxy anisole) to protect the active ingredient from oxidative degradation.
The statins that can be used in the compositions described in conjunction with the present invention are defined on the basis of their biopharmaceutical class. The biopharmaceutical classification system (BCS) classifies pharmaceutically active substances with regard to their expected bioavailability. The statins used in the compositions according to the invention are classified in biopharmaceutical class II and have a low solubility in the physiological system with a high permeation capacity. Absorption is controlled by the solubility and/or dissolving rate of the pharmaceutical drugs.